ArticleGastroenterology2015
Signal Transducer and Activator of Transcription 3, Mediated Remodeling of the Tumor Microenvironment Results in Enhanced Tumor Drug Delivery in a Mouse Model of Pancreatic Cancer.
Article in Gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 1 of them a synthesis that pooled it.
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Who cites it
115 citing papers in PubMed, 1 synthesis or guideline pooled it, 189 citations in OpenAlex.
- Signaling pathway mechanisms in pancreatic ductal adenocarcinoma tumor microenvironment and emerging targeting strategies for improved prognosis.Oncology reviews · 2026Pooled it
- Conversational Artificial Intelligence-Enabled Precision Oncology Reveals Context-Specific TGFβ and JAK/STAT Alterations in Pancreatic Cancer.medRxiv : the preprint server for health sciences · 2026Article
- Engineered Cell Membrane-Coated Nanoparticles: A New Strategy for Pancreatic Cancer Therapy.ACS pharmacology & translational science · 2026Review
- Role of cancer-associated fibroblast-derived exosomes in pancreatic cancer: clinical therapeutic potential and targeting challenges.Frontiers in immunology · 2026Review
- DUSP6 is upregulated in metastasis and influences migration and metabolism in pancreatic cancer cells.Scientific reports · 2025Article
- OZ-001 Suppresses the Growth of Triple-Negative Breast Cancer and Pancreatic Cancer by Targeting STAT3 Phosphorylation and the Calcium Signaling Pathway.Biomolecules & therapeutics · 2025Article
- CCN1 Enhances Tumor Immunosuppression through Collagen-Mediated Chemokine Secretion in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- SMAD4 and KRAS Status Shapes Cancer Cell-Stromal Cross-Talk and Therapeutic Response in Pancreatic Cancer.Cancer research · 2025Article
- Review
- Navigating the Clinical Landscape of Liposomal Therapeutics in Cancer Treatment.Pharmaceutics · 2025Review
- Desmoplastic reaction in the microenvironment of head and neck and other solid tumors: the therapeutic barrier.Therapeutic advances in medical oncology · 2025Review
- The role of inflammatory factors in the tumor microenvironment of pancreatic cancer.Frontiers in immunology · 2025Review
- Unveiling the resistance to therapies in pancreatic ductal adenocarcinoma.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024Review
- QuantifyingBiophotonics discovery · 2024Article
- PQR309, a dual PI3K/mTOR inhibitor, synergizes with gemcitabine by impairing the GSK-3β and STAT3/HSP60 signaling pathways to treat nasopharyngeal carcinoma.Cell death & disease · 2024Article
- Discovery of the Highly Selective and Potent STAT3 Inhibitor for Pancreatic Cancer Treatment.ACS central science · 2024Article
- JAK/STAT3 represents a therapeutic target for colorectal cancer patients with stromal-rich tumors.Journal of experimental & clinical cancer research : CR · 2024Article
- Recent advances in drug delivery and targeting for the treatment of pancreatic cancer.Journal of controlled release : official journal of the Controlled Release Society · 2024Review
- The oncogenic mechanisms of the Janus kinase-signal transducer and activator of transcription pathway in digestive tract tumors.Cell communication and signaling : CCS · 2024Review
- Transcription factors in fibroblast plasticity and CAF heterogeneity.Journal of experimental & clinical cancer research : CR · 2023Review
55 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsA hallmark of pancreatic ductal adenocarcinoma (PDAC) is the presence of a dense desmoplastic reaction (stroma) that impedes drug delivery to the tumor. Attempts to deplete the tumor stroma have resulted in formation of more aggressive tumors. We have identified signal transducer and activator of transcription (STAT) 3 as a biomarker of resistance to cytotoxic and molecularly targeted therapy in PDAC. The purpose of this study is to investigate the effects of targeting STAT3 on the PDAC stroma and on therapeutic resistance.
methodsActivated STAT3 protein expression was determined in human pancreatic tissues and tumor cell lines. In vivo effects of AZD1480, a JAK/STAT3 inhibitor, gemcitabine or the combination were determined in Ptf1a(cre/+);LSL-Kras(G12D/+);Tgfbr2(flox/flox) (PKT) mice and in orthotopic tumor xenografts. Drug delivery was analyzed by matrix-assisted laser desorption/ionization imaging mass spectrometry. Collagen second harmonic generation imaging quantified tumor collagen alignment and density.
resultsSTAT3 activation correlates with decreased survival and advanced tumor stage in patients with PDAC. STAT3 inhibition combined with gemcitabine significantly inhibits tumor growth in both an orthotopic and the PKT mouse model of PDAC. This combined therapy attenuates in vivo expression of SPARC, increases microvessel density, and enhances drug delivery to the tumor without depletion of stromal collagen or hyaluronan. Instead, the PDAC tumors demonstrate vascular normalization, remodeling of the tumor stroma, and down-regulation of cytidine deaminase.
conclusionsTargeted inhibition of STAT3 combined with gemcitabine enhances in vivo drug delivery and therapeutic response in PDAC. These effects occur through tumor stromal remodeling and down-regulation of cytidine deaminase without depletion of tumor stromal content.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.